Erythromycin versus cefadroxil in the treatment of skin infections.

Erythromycin is often overlooked for the treatment of skin and skin structure infections. We evaluated the efficacy and safety of erythromycin particles in tablets and of cefadroxil in 164 patients with skin infections; both treatments were given as 500 mg twice daily. One hundred percent of erythromycin and 96% of cefadroxil patients were clinically cured or improved, and 98% of susceptible pathogens were eradicated in both groups. Only three erythromycin patients and one cefadroxil patient left the study early because of GI-related adverse events. Erythromycin, therefore, was as effective and safe as cefadroxil in the treatment of mild-to-moderate skin infections.

The effects of estrone (Ogen) on spinal bone density of postmenopausal women.

The effects of cyclical treatment with estrone sulfate (0.3, 0.625, or 1.25 mg), plus calcium carbonate, on spinal trabecular bone density were compared with placebo in 120 postmenopausal women in this 2-year, multicenter, double-blind study. While the placebo and 0.3-mg treatment groups lost bone density (-3.6% and -5.1%), the 0.625- and 1.25-mg treatment groups experienced no significant change from baseline at 24 months (-0.8% and +0.7%). The 1.25-mg treatment group was significantly different from the placebo group at 12, 18, and 24 months. Although the 0.625-mg treatment group was significantly different from the placebo group only at 18 months, the data suggest that 0.625 and 1.25 mg of estrone sulfate had different effects than placebo and 0.3 mg of estrone sulfate and, given with supplemental calcium, are effective doses for the prevention of spinal bone loss.

Effect of cyclic estrone sulfate treatment on lipid profiles of postmenopausal women with elevated cholesterol levels.

The effects of two doses of cyclic unopposed estrone sulfate therapy on the lipid profiles of 153 healthy postmenopausal women with baseline total cholesterol levels above 219 mg/dL were compared in a multicenter, double-blind, placebo-controlled study. Patients were assigned randomly to one of three treatment groups: estrone sulfate 0.625 mg (N = 59) or 1.25 mg (N = 43), or placebo (N = 51). The median baseline total cholesterol levels of the three treatment groups were 262, 269, and 262 mg/dL, respectively. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and the HDL/LDL ratio were assessed after 6, 9, and 12 months of treatment. There was a significant monotonic dose-response relationship of estrone sulfate in raising HDL levels, lowering LDL levels, and raising the HDL/LDL ratio at all intervals measured. These results indicate that estrone sulfate is effective in creating a beneficial change in the lipid profile of postmenopausal women with elevated baseline total cholesterol.

Mechanism of glycosuria during volume expansion superimposed on subthreshold glucose loading.

In order to elucidate the mechanism of glycosuria, clearance and micropuncture studies were performed in 19 dogs before and after subthreshold glucose loading and again after superimposition of extracellular volume expansion. Subthreshold glucose loading inhibited proximal sodium reabsorption and increased proximal glucose reabsorption, demonstrating dissociation between net sodium and glucose transport. Glucose delivery out of the proximal convoluted tubule was greatly increased by the combined effect of increased filtered load of glucose and reduced fractional proximal fluid reabsorption. There was a remarkable compensatory increase in glucose reabsorption in the segment between late proximal tubule and distal tubule (intermediate segment) and glycosuria did not occur. When 10% extracellular volume expansion was superimposed on the ongoing subthreshold glucose loading, absolute proximal glucose reabsorption was inhibited. This led to an additional increase in glucose delivery to the intermediate segment, but glucose reabsorption in this segment failed to increase further and overt glycosuria eventually developed. Thus the intermediate segment possesses some capacity to reabsorb glucose when glucose load is increased, and glycosuria develops only when the glucose reabsorptive capacity of this segment is exceeded. We conclude that the intermediate segment serves as the "buffer zone" of renal glucose transport and plays an important role in the regulation of urinary glucose excretion.

Beta-blocking effect of single oral doses of carteolol.

Carteolol is a nonselective beta-adrenergic blocking agent with intrinsic sympathomimetic activity. The duration of beta blockade after single oral doses of carteolol was studied in normal men for 72 hr by determining the heart rate response to an external stimulus, bolus intravenous isoproterenol, and an internal stimulus (graded treadmill exercise designed to achieve 85% of the subjects' maximal heart rate in 12 min). Each subject first received 5 mg of carteolol and then, at 3-wk intervals, 2.5, 15, and 60 mg carteolol and placebo in a randomized, double-blind fashion. Beta blockade was maximal 1 to 2 hr after dosing and the heart rate response to isoproterenol and exercise remained less (P less than 0.05) than placebo responses for the 72 hr after each dose of carteolol. The double product (maximal exercise heart rate x systolic blood pressure during the twelfth minute of exercise) was below (P less than 0.05) baseline values for 24 hr after all doses, for 48 hr after 15 mg, and for 72 hr after 60 mg of carteolol.

Renal phosphate adaptation in uraemic dogs with a remnant kidney.

1. Clearance and micropuncture studies were performed in 27 dogs made uraemic by segmental infarction to examine the factors responsible for phosphate adaptation in chronic renal failure. 2. The animals were studied before and after extracellular volume expansion to 10% of body weight in the presence and absence of parathyroid glands. The results were compared with 19 normal dogs studied under similar experimental conditions. 3. In the dogs with a remnant kidney and intact parathyroids adaptation of phosphate transport was evident, with a high fractional excretion of phosphate. Thyroparathyroidectomy 3 days before study in the dogs with a remnant kidney and moderate renal failure reduced fractional excretion of phosphate to near normal values, indicating a major role of parathyroid hormone in phosphate adaptation. Extracellular volume expansion in these thyroparathyroidectomized uraemic dogs led to an exaggerated phosphaturic response with fractional excretion of phosphate returning towards the value in the uraemic dogs with intact parathyroid glands. Thus acute extracellular volume expansion could also contribute to the increase in fractional phosphate excretion, but extracellular volume probably plays a relative minor role in the adaptation of phosphate excretion. 4. With more advanced renal failure fractional excretion of phosphate remained high, even after thyroparathyroidectomized, indicating that parathyroid hormone-independent factors become important for phosphate adaptation in the advanced stage of renal failure. The nature of parathyroid hormone-independent changes in fractional phosphate reabsorption in chronic renal failure remains unknown. 5. Proximal tubular fluid/plasma ultrafiltrate phosphate ratios were high in all groups of dogs with a remnant kidney regardless of thyroparathyroidectomy or the degree of renal failure. The non-specific nature of the proximal tubule pattern of phosphate transport indicates that phosphate adaptation is primarily determined by alterations in phosphate transport at a site distal to the proximal convoluted tubule. Alternatively, deep nephrons may play a greater role in determination of the overall phosphate adaptation in the chronically diseased kidney.

Effect of volume expansion on renal glucose transport in normal and uremic dogs.

Proximal and distal tubule micropuncture studies were performed in normal and uremic remnant-kidney dogs to examine the tubule mechanism of glucose reabsorption before and after 10% extracellular volume expansion. In normal dogs volume expansion markedly inhibited glucose reabsorption in the proximal convoluted tubule, but the ensuing increase in further distal glucose delivery was nearly completely reabsorbed in the intermediate segment (between late proximal tubule and distal tubule). In the uremic, remnant-kidney dogs, glomerulotubular balance for glucose was well maintained in the proximal convoluted tubule despite an adaptive increase in nephron filtration rate. Volume expansion markedly increased glucose delivery out of the proximal convoluted tubule and an incomplete glucose reabsorption in the intermediate segment led to glycosuria. When glucose delivery to the intermediate segment was increased to a comparable degree by subthreshold glucose loading in hydropenic normal dogs, glucose reabsorption in this segment was virtually complete, suggesting that in the volume-expanded uremic dogs glucose reabsorptive capacity in the intermediate segment was reduced. Thus, the intermediate segment appears to play a significant role in the fine regulation of urinary glucose excretion.

Effect of phosphate deprivation on renal phosphate transport in the dog.

In order to examine the role of dietary intake of phosphate in regulating renal phosphate transport, clearance and micropuncture studies were performed in 25 dogs with various duration of phosphate deprivation induced by low phosphate diet and aluminum hydroxide gel. In phosphate deprivation of 17-41 days duration, the phosphaturic response to extracellular volume expansion (ECVE) was blunted in the intact group and was virtually abolished in the acutely thyroparathyroidectomized (TPTX) group. With longer phosphate deprivation of 53-110 days, no phosphaturia occurred after ECVE or administration of parathyroid hormone (PTH), even with intact parathyroids. These alterations in phosphaturic responses did not correlate with the plasma phosphate but rather with the duration of phosphate deprivation. Fractional proximal tubule phosphate reabsorption was enhanced in phosphate deprivation and the proximal tubule fluid-to-ultrafilterable phosphate ratio appeared to be a good index for the degree of phosphate deprivation. Acute infusion of phosphate to raise plasma phosphate slightly above normal did not completely restore the responsiveness to ECVE. It is concluded that the adaptive response to phosphate deprivation occurs in both proximal and distal nephron segments and that factors other than plasma phosphate are primarily responsible for such an adaptation.